The hepatitis B surface antigen (HBsAg) consists of a group-specific determinant, a, and at least two subtype systems, d/y and w/r. The d/y and w/r specificities behave in an allelic manner and they represent the expression of distinct genotypes of HBV. Heretofore, protection against HBV infection has been ascribed to antibodies directed toward the common group determinant, a. Protectivity by the anti-subtype antibodies has not been assessed. The availability of monoclonal antibody to determinant, d, made this evaluation possible. A chimpanzee was intravenously inoculated with the standard HBV inoculum (adw subtype, 10,000 CID-50) which had been preincubated with 225-fold excess of the monoclonal anti-d. After the inoculation, the chimpanzee did not express any serological markers for HBV infection for a period of 44 weeks. At the end of that period, the chimpanzee was challenged with the standard inoculum and found to be susceptible. Hence, neutralization was achieved by this monoclonal anti-d.